By Rob Waters
Mick Phillips didn't think much about it when he started coughing a lot in the fall of 2009. He'd been doing a lot of yard work at his home in Appleton, Wis., and thought he might be reacting to leaf mold. In fact, he had stage 3 lung cancer. Though his doctors didn't tell him this, his odds of living for five years were vanishingly small.
Chemotherapy and radiation worked for a time. But his doctor warned him each round would be less effective.
So Phillips came up with a new plan: Cuba.
Even as the US-Cuba relationship changes, bringing a growing numbers of tourists, the island remains in many ways frozen in time; when Phillips was last there in the spring, he was driven around by a cabbie in a '55 Buick. But a striving, modern biotech enterprise thrives in Cuba, too. It's a legacy of the US embargo: With drugs from the US unavailable, Cuba had to develop its own pharmaceutical industry. Among its biggest accomplishments is a novel treatment for lung cancer called CimaVax.
The Cuban data on CimaVax is promising, prompting an American oncologist at Roswell Park Cancer Institute in Buffalo, N.Y., to make plans to submit an application to the Food and Drug Administration this summer for a 70-patient trial to test the drug's safety -- in what would likely be the first-ever US clinical trial of a Cuban therapy.
For now, though, CimaVax is out of reach -- at least for most patients. Doctors can't prescribe the drug in the US because it hasn't been FDA approved. And with an embargo still in place, American patients can't legally fly to Havana for treatment.
That did not stop Phillips.
In July 2011, two weeks after completing a second round of chemotherapy, he and his wife, Maya, boarded a plane for Lima to get CimaVax treatment in Peru, where it's legal. Later, they'd come up with a way to sneak CimaVax into Wisconsin from Cuba.
His oncologist hadn't heard of the drug before Phillips told him about it. Five and a half years later, he's a believer.
Phillips, 79, is one of a small number of intrepid lung cancer patients from the US who has traveled to Cuba to get CimaVax or, more recently, a second cancer treatment called Vaxira that works in a different way.
"Outside of divine intervention, this guy shouldn't be living right now," Dr. Timothy Goggins said. "If you believe in God, it's God. If you believe in science, it's CimaVax."
"Outside of divine intervention, this guy shouldn't be living right now. If you believe in God, it's God. If you believe in science, it's CimaVax," said Doctor Timothy Goggins.
Phillips, 79, is one of a small number of intrepid lung cancer patients from the US who has traveled to Cuba to get CimaVax or, more recently, a second cancer treatment called Vaxira that works in a different way. The patients, not all of whom have done well on the drug, share information through social media, especially a website for cancer patients.
"We find CimaVax to be incredibly exciting," said Dr. Kelvin Lee, the Buffalo oncologist planning the US study of the treatment. "It's inexpensive, it's easy to give, and it has very little toxicity. And the Cubans have done a whole series of clinical trials which have shown that CimaVax increases overall survival."
A Cuban study of 405 patients published earlier this year in the journal Clinical Cancer Research found that those who were given CimaVax lived about three months longer than those in a control group who got standard care only. More importantly, after five years, 23 percent of the patients who took the vaccine were still alive. None in the control group survived that long.
Taking a risk to beat a tough foe
CimaVax aims to mobilize the body's immune system to fight cancer by reducing levels of epidermal growth factor, or EGF, a protein that fuels the proliferation of cells, including cancer cells. Several cancer drugs already marketed in the US -- including Erbitux, Tarceva, Iressa and Tykerb -- also target EGF, but in a different way. All of them cause more frequent and serious side effects than CimaVax, according to Lee.
CimaVax was approved by Cuban medical regulators in 2008 and is also approved in Venezuela and Peru, with clinical trials underway in Europe and Malaysia. Lee has made 11 trips to Cuba over the past four years to meet with scientists from the Cuban Institute for Molecular Immunology, which developed the vaccine. He calls the institute's manufacturing facilities "world class."
Mick Phillips had pretty modest goals when he and Maya decided to make the trip to Peru and give CimaVax a try.
His first post-chemotherapy remission had lasted 10 months before the cancer returned; his hair grew back and he returned to his job managing a company that sells and repairs industrial pumps. But Goggins, his oncologist, had warned that future remissions would be much shorter. Phillips hoped the drug would stretch them out.
Goggins didn't tell him this part: "He probably had six months to one year [to live] at that point, depending on his response to chemotherapy. And after a recurrence, survival for five years is zero percent."
Despite those odds, "I had no reason to think [the Cuban drug] was a good option," Goggins said. "But they researched it and decided to do it. I don't try and stop people from doing things like that."
In Lima, Phillips got one round of chemotherapy and then was injected with CimaVax every two weeks -- one shot in each shoulder, one shot in each hip. The treatment caused minimal side effects, mostly a mild fever and chills that once left him shaking and clutching surgical gloves filled with hot water. After two months, he and his wife, a native Peruvian, returned home with supply of CimaVax in their suitcase.
Between travel and drug costs, Phillips estimated they spent $50,000 for that first year of treatment.
Back in Wisconsin, Phillips found a nurse friend to come to his home each month to inject him with CimaVax. Meanwhile, Maya continued to do research and found that they could get the treatment in Cuba for a lot less than in Peru.
Mick Phillips has now made five trips to Havana, some with Maya, some alone, and the most recent one with his grandson. He gets treated at Centro Internacional de Salud La Pradera, a hotel-like hospital for foreign medical tourists located on the outskirts of Havana, by Dr. Ruben Elzaurdin, chief of oncology services.
On each trip, Phillips brings gel ice packs and cash -- Americans can't use ATMs or credit cards in Cuba due to the continuing embargo. At the end of each stay, he packs vials of CimaVax with the chilled gel packs into an insulated lunch box to make the trip home. He flies to Toronto, then drives 11 hours back to Wisconsin.
He does not tell US customs agents that he's carrying medicine made in Cuba.
Phillips continues to see Goggins, who performs regular scans and has found no sign of cancer returning.
More than one way to kill a cancer cell
The idea for CimaVax was born in Havana in the 1980s.
Lee, the Buffalo oncologist, says the Cuban medication -- which is called a vaccine, though it's a treatment -- is quite different from the immunology-based cancer therapies developed in the US.
At the time, scientists were unraveling the role of the EGF system, one of the key forces driving the uncontrolled proliferation of cells that occurs in cancer. They knew this proliferation is enabled when ligands -- specialized molecules that circulate in the blood and other places -- bind with EGF receptors on the surface of cells.
"In cancer cells you have a thousand times more EGF receptors than in normal cells. We knew that more over-expression leads to worse prognosis," said Gisela Gonzalez, a scientist who worked on CimaVax for decades as part of a team at the Center for Molecular Immunology in Havana before moving to Miami three years ago.
Researchers around the world were looking for ways to prevent ligands and EGF receptors from binding. In the US and Europe, most targeted the receptor side of this pairing, leading to the development of so-called EGFR inhibitors, now on the market to treat certain types of breast, colon, and lung cancer.
The Cuban scientists decided to take a different tack: "We thought, 'Why not try to block the ligand, the protein in our blood, instead of the receptor on the cells,'" Gonzalez said.
Lee, the Buffalo oncologist, says the Cuban medication -- which is called a vaccine, though it's a treatment -- is quite different from the immunology-based cancer therapies developed in the US.
"Most initiate an immune response that kills cancer cells," Lee said. "CimaVax is designed to initiate an immune response that depletes EGF out of the bloodstream."
Although extensive testing has been done only in lung cancer, CimaVax also has the potential to be used against other EGF-dependent solid tumors, including some forms of breast, prostate, colon, and head and neck cancer, Lee said. And because it is relatively inexpensive to produce, doesn't need to be kept frozen, and causes few side effects, it can be used in primary care clinics by family doctors, not specialists.
That also raises another possibility: that the vaccine could be used to prevent recurrence. With lung cancer screening gaining wider use, more people are going to be found with early stage cancer and will have their tumors removed.
"These people are technically cured." Lee said, "But we know that 50 percent of them will get a second lung cancer within five years. If we could actually vaccinate those patients with CimaVax and reduce their risk of a relapse, that would be a significant step forward."
"If we could actually vaccinate those patients with CimaVax and reduce their risk of a relapse, that would be a significant step forward," said Dr. Kelvin Lee.
To develop CimaVax, Gonzalez and her colleagues devised a biological compound that could effectively interfere with the binding process and tested it in mice and, later, monkeys. They learned that it worked to reduce levels of EGF in the blood. And lower levels of EGF seemed to be correlated with longer survival in animals with cancer.
The first group of 10 people with lung cancer was treated in 1994 to test the safety of CimaVax. Since then, about 4,000 people have taken the drug.
The other lung cancer therapy that American patients travel to Cuba to get was jointly developed by the Center for Molecular Immunology and researchers from Buenos Aires University in Argentina and was approved in Cuba 2013. Called Vaxira, it targets a specific antigen that is attached to lung cancer cells and recruits the army of cells in the body's immune system to attack it.
Vaxira is "completely novel and captivating," said Dr. Thomas Rothstein, an oncologist and research scientist recently recruited to head up a new Center for Immunobiology at Western Michigan University School of Medicine.
Rothstein spent the last decade as a senior investigator at the Feinstein Institute for Medical Research in Manhasset, N.Y., and has maintained a research collaboration with a team at the CIM in Havana since 2008. He visits the country frequently.
"It's amazing what they accomplish there, working in difficult circumstances and with limited resources," he said.
"It's amazing what they accomplish there, working in difficult circumstances and with limited resources," said Dr. Thomas Rothstein.
A small number of American patients have gone to Cuba to take Vaxira. Many more have taken CimaVax. According to Gonzalez, the longest-living patient is a young man from Spain who has survived for 10 years. Mick Phillips is believed to be the longest-surviving American, a distinction he's quite proud of.
"I'm elated that it's done more that we ever expected it to," Phillips said. "I think I'll die of something different than lung cancer -- probably my hard head."
In truth, said Phillips, a lifelong smoker, the biggest threat to his health is another lung disease, COPD, which recently led to a bout of pneumonia. He has since recovered. "I'm back to doing two flights of stairs," he said, "but not carrying a laundry basket."
Evangelist with a cause
On Inspire, the patient social network, Phillips is a bit of an evangelist for CimaVax, sharing his experience with other cancer patients and letting them know what he learns. He knows of patients who have had poor results, including one who died about a month after getting treated.
But he's persuaded others to gamble on Cuban medicine.
One regular reader of the website, a technology worker who asked to remain anonymous to guard his family's privacy, was inspired by Phillips's experience to take his mother, a retired physician from Pakistan, to Cuba. They spent a week this summer in Havana while she was treated with CimaVax.
A year of chemo with a variety of drugs had weakened his mother, who is 78. Worst, none of it seemed to reduce a fluid build-up in her lungs that made it hard to catch her breath. For the better part of the past year, she'd been having regular lung taps -- a painful procedure that uses a needle through the ribs to suck fluid out of the lungs.
"They pulled a liter of fluid from her lungs every two weeks without fail," the son said.
They left Havana with an eight-month supply of CimaVax at a cost of about $10,000 -- a significant amount, but a fraction of what new cancer drugs cost in the US. Since no medical professional would agree to be liable for a drug that's not approved in the US, the son has been giving his mother her bi-weekly injections himself.
She said he's pretty good with a syringe. "He learned from Google," she said.
Six days ago, she had her first lung tap since she went to Cuba. Nurses pulled out only a fraction of the amount of fluid they had in the past, her son said.
"I feel hopeful," the mother said. "It's better than chemo because there are no side effects. I feel better than before."